Aromatic azomethines

ABSTRACT

Novel azomethines are obtained when reacting a tertiary amine with an aromatic aldehyde or ketone having in orthoposition an activated methoxy group. These azomethines are capable of ring closure to yield a benzofurane and said tertiary amine. The benzofuranes are optical brighteners, tranquilizers or intermediates for optical brighteners, fluorescent dyestuffs, scintillators, sensibilizers for electrophotographic coatings.

This application is a division of application Ser. No. 567,357 filedApr. 11, 1975 , now U.S. Pat. No. 3,994,879, which is a division ofapplication Ser. No. 427,016 filed Dec. 13, 1973 now U.S. Pat. No.3,892,807.

The present invention relates to the preparation of furan compounds.

It has been proposed to prepare compounds of the general formula (1)##STR1## wherein A represents an aromatic mono- or polynuclear ringsystem which is condensed with the furan nucleus by two adjacent carbonatoms as indicated, R represents a hydrogen atom, an optionallysubstituted molecular alkyl group of 1 to 4 carbon atoms or anoptionally substituted phenyl group and D represents an organic radicalbeing conjugated with the furan radical, by splitting off water, using astrongly basic condensating agent, from a compound of the formula (2)##STR2## wherein A and R are defined as above and D' represents anorganic radical which is conjugated with the double bonds of the furannucleus after ring closure (U.S. pat. application Ser. No. 279.645)

The present invention provides a process for the preparation ofcompounds of the general formula (1), which comprises preparingcompounds of the general formula (4) ##STR3## from compounds of thegeneral formula (2) and from amines of the general formula (3)

    E--NH.sub.2                                                ( 3)

and splitting off an amine of the formula (3) from the compounds offormula (4) in the presence of strongly basic condensation agents instrongly polar solvents under ring closure.

In the formula (3) E stands for an aliphatic, aromatic carbo-orheterocyclic radical which is linked to the azomethine nitrogen atom viaa tertiary carbon atom. In the formula (4) A, R and D' have the meaningsgiven in the general formula (1) and (2).

The azomethines of the general formula (4) are prepared in a mannerknown per se at ambient or elevated temperature and, optionally, usingsolvents or diluents, for example, by heating them in toluene,chlorobenzene or other aromatic solvents, optionally in the presence ofan acidic catalyst, such as a mineral acid or a strong organic acid,such as p-toluenesulfonic acid.

Suitable amines of the formula (3) are, for example aniline, α- andβ-naphthylamine and the nucleus-substituted products of these aromaticamines or as an aliphatic amine the tertiary butyl amine. As theseamines are split off during this reaction, the presence of substituentsis, generally not advantageous in this case. However, for example aminesof the general formula (3') ##STR4## may carry substituents Z which donot hamper the reaction, for example halogen, especially chlorine atoms,alkyl or alkoxy group having 1 to 4 carbon atoms or hydroxyalkyl groupshaving 2 to 4 carbon atoms. Among the amines of the general formula (3)mentioned above, the anilines of the general formula (3') in which Zstands for a hydrogen atom or a chlorine atom, are preferred. Amongthese, especially the unsubstituted aniline is preferred (Z═H).

In the process of the invention, there are preferably prepared compoundsof the formula (1') ##STR5## by the intramolecular ringclosure of acompound of the general formula (4') ##STR6## in strongly polar organicsolvents under the action of strongly alkaline condensating agents.

The compounds of the general formula (4') are synthesized by reactingcompounds of the general formula (2') ##STR7## with aniline according tothe process mentioned above. In the general formulae (1') and (2') and(4'), A is defined as above. The other symbols are defined as follows:

B represents a direct bond or a continuously conjugated chain of carbonatoms, which is, wholly or in part, a constituent of a carbocylic orheterocylic ring system in which one or more than one carbon atoms maybe replaced by hetero atoms, especially a nitrogen atom, and the doublebonds are placed in such a manner that the molecule is completelyconjugated;

B' is a direct bond or a continuously conjugated chain of carbon atomswhich is, wholly or in part, a constituent of a carbocylic orheterocyclic ring system in which one or more than one carbon atoms maybe replaced by hetrero atoms, especially by a nitrogen atom, and thedouble bonds are placed in such a manner that a molecule, which iscompletely conjugated, is formed after ring closure,

Y represents an aryl, an optionally modified carboxy orsulpho group, anacyl, sulphonyl or nitro group, or if

B' contains an aromatic ring, also a hydrogen atom.

One or more substituents Y may be bound to the carbo- or heterocyclicring systems of B and B', but also further halogen atoms, especiallychlorine atoms. Alkyl and/or alkoxy groups, especially lower alkyland/or alkoxy groups may also be linked to B', and accordingly to B, butonly if B' possesses electron-accepting groups, the electron-acceptinginfluence of which on the CH₂ --group overcompensates the effect of thesaid groups as electron-donors.

Suitable substituents which may be linked to A are of course only thosewhich do not hamper nor heavily disturb the reaction. Halogen atoms,alkyl, alkylene, aryl and alkoxy groups are preferred. But, alkenyl,alkinyl, aralkyl, aralkenyl, aralkinyl, optionally modified carboxy orsulfo groups, aryl, and sulfonyl groups may also be linked to A.Suitable substitutents are especially those which contain aliphaticradicals having 1 to 4 carbon atoms and as aryl radical a phenylradical. All substituents are not allowed to carry hydrogen atoms whichcan be replaced by metal atoms in a more easy or similarly easy manneras compared with the hydrogen atoms of the CH₂₋₋ group in the formulae(4), (4') or the following formula (4").

Functionally modified carboxy groups are, firstly, their salts withcolourless cations, alkali metal ions or ammonium ions being preferred.There may, furthermore, be mentioned, the cyano group (nitrile group),the carboxylate group or the carboxylic acid amide group. Carboxylategroups are especially those of the general formula COOR¹, wherein R¹ isa phenyl radical or a lower alkyl group optionally having a branchedchain, which radicals may contain further substituents, for example, apreferably low-molecular dialkylamine, lower trialkylammonium or alkoxygroup in which dialkylamino or trialkylammonium groups two alkyl groupsmay be replaced by a ring, such as is in the morpholino or piperidinogroups. A carboxylic acid amide group is especially one of the formulaCONR² R³ wherein the radicals R² and R³ each represents a hydrogen atomor a lower alkyl group which may be, optionally, substituted, which mayalso form together with the nitrogen atom a hydroaromatic ring, whichoptionally, may carry furtherhetero atoms, such as oxygen or nitrogenatoms, for example, a piperidino or morpholino group.

Functionally modified sulpho groups are, by analogy with the descriptiongiven above, the salts with colourless cations, preferably alkali metalions or ammonium ions, and derivatives in which the S0₂ -group is linkedto a hetero atom, as to be found in the sulphonate group and in thesulphonamide group. A sulphonate group is especially one of the formulaS0₂ OR¹ wherein R¹ is defined as above and a sulphonamide group is oneof the formula S0₂ NR² R³ wherein R² and R³ are defined as above.

An acyl group is especially one of the formula COR⁴ wherein R⁴ ispreferably lower alkyl or a phenyl radical which may optionally besubstituted.

A sulphonyl radical is especially one of the formula S0² R⁵ wherein R⁵represents a lower alkyl or a phenyl radical, optionally substituted,each of which may carry as substituents preferably a lower dialkylamino,lower trialkyl ammonium, acylamino (each as defined above) or sulphogroup.

The present invention also provides a process for preparing a compoundof the general formula (1") ##STR8## which comprises splitting off aminefrom compounds of the general formula (4") ##STR9## i.e. the radical Dor D' contains itself a furan radical or its precursor.

The radicals A, B, B', E and R of these formulae have the samedefinitions as given above.

The preparation of compounds of the general formula (4") (E = preferablyphenyl and B' = preferably p,p'-diphenyl) is carried out in a manneranalogous to the preparation of the compounds of the general formulae(3) and (3'), for example from the corresponding dialdehydes ordiketones (2") ##STR10##

The precusors (2), (2') and (2") are reaction products of compounds ofthe general formulae (5) ##STR11## in which M represents an alkali metalor an alkaline earth metal cation and A and R are as defined in thegeneral formula (1), with compounds of the general formula (6). (6') or(6") ##STR12## in each of which X represents a radical which can easilybe split off as anion, preferably the anion of an inorganic acid,preferably of a hydrohalic acid and D', B', and Y are as defined in thegeneral formula (2) and (2'), in an organic solvent.

The alkali metal or alkaline earth metal salts (5) may, for example, bethe following:

Salicylic aldehyde, 5-chloro-salicylic aldehyde, 3,5-dichloro-salicylicaldehyde, 3-bromosalicylic aldehyde, 4-bromo-salicylic aldehyde,5-bromosalicylic aldehyde, 3,5-dibromosalicylic aldehyde,3-fluoro-salicylic aldehyde, 3-chloro-salicylic aldehyde,6-methyl-salicylic aldehyde, 5-chloro-6-methylalicylic aldehyde,3-methyl-salicylic aldehyde, 5-methylsalicylic aldehyde,4-methyl-salicylic aldehyde, 5-chloro-4-methyl-salicylic aldehyde,6-ethyl-salicylic aldehyde, 4-ethyl-salicylic aldehyde,3,5-dimethyl-salicylic aldehyde, 4,5-dimethyl-salicylic aldehyde,3-phenyl-salicylic aldehyde or 5-phenyl-salicylic aldehyde,2-hydroxy-acetophenone,2-hydroxy-4-chloro-acetophenone,2-hydroxy-benzophenone, 2-hydroxy-4,5-dimethyl-acetophenone or2-hydroxy-(α-methoxy)-acetophenone.

As compounds of the general formula (6), (6') and (6") there may bementioned, for example, the following substances: benzylchloride,p-cyano-benzylchloride, p-carbomethoxy-benzylchloride,p-nitro-benzylchlorine, p-trifluoromethyl-benzlchloride,o-trifluoromethyl-benzyl-chloride, 2,3,4,5,6-pentafluoro benzylchloride,m-trifluoromethyl benzylchloride, 4-bromomethyl benzosulphonicacid-dimethylamide, 2-chloromethyl-4-nitrophenol,4-chloromethyl-α-phenyl-anisol,5-bromoethyl-3-(4-tolyl)-1,2,4-oxadiazole, 5-bromo-pentadiene-(1,3),1-cyano-5-chloro-pentadiene-(1,3), cinnamyl chloride, cinnamyl bromide,1,1-diphenyl-2-bromo methyl-ethylene, 2-bromoethyl-benzofuran,3-bromoethyl-benzofuran, 3-bromomethyl-thiophene, 4,4'-bischloromethyl-diphenyl, 4,4'-bischloromethyl-diphenyl ether,2-bromomethyl-4,5-benzo-benzofuran, 2-chloromethyl-benzoxazole,5-chloro-1-(2'-benzoxazoly)-pentadiene-(1,3),2-chloromethyl-4,5-benzo-benzoxazole,2-chloromethyl-5,6-benzo-benzoxazole,2-chloromethyl-6,7-benzo-benzoxazole,2-chloro-methyl-5-methyl-benzoxazole,2-chloromethyl-5,6-dimethyl-benzoxazole,2-bromomethyl-5-carbomethyoxy-furan, 2-bromo-methyl-5-cyanofuran,2-bromomethyl-5-carbomethoxy-thiophene, 2-bromomethyl-5cyano-thiphene,2-chloromethyl-pyridine, 3-chloromethyl-pyridine,4-chloromethyl-pyridine, 2-chloromethyl-quinoline,1-bromo-methyl-4-cyano-naphthalene,1-bromomethyl-4-carbomethoxy-naphthalene and chloroacetonitrile.

Intermediate of the formula (4) which can be prepared according to theinvention are, for example, the following: ##STR13##

The ring closure reaction of the invention is carried out in stronglypolar, neutral to alkaline organic solvents which are free form atomscapable of being replaced by alkali metals, especially hydrogen atoms.There may be used, for example, as solvents alkylated acyl amides of thegeneral formula (8) ##STR14## wherein "Alk" is a lower alkyl grouphaving not more than 4 carbon atoms, "Acyl" is the radical of alow-molecular carboxylic acid having not more than 4 carbon atoms,especially formic acid and acetic acid, or the phosphoric acid radical,w indicates the basicity of the acid, i.e., how many base equivalentsthe acid can bind, and v is zero or the numbers 1 or 2, preferably 1 or2, especially 2.

The following solvents may, for example, also suitably be used:tetramethyl urea, N-methyl-pyrrolidone, acetonitrile or pyridine.

The solvents, however which are of the general formula (7) are espciallyimportant, among which those are preferred in which v is 2. Dimethylformamide, hexamethyl-phosphoric acid trisamide, diethyl-formamide anddimethyl-acetamide are of special interest.

The solvents can be used separately or in admixture with one another.

For the condensation reaction, strongly basic condensation agents arerequired, which are, for example, the strongly basic alkaline earthmetals and especially alkali metal compounds, for example, thehydroxides, amides, hydrides, sulphides, alcoholates and strongly basicion exchangers thereof, and further aluminum hydride, nitride oralcoholates.

The alcoholates to be used are especially derived from linear-chain,branched-chain or cyclic lower aliphatic alcohols having up to 8 carbonatoms, preferably from linear-chain alkanols having from 1 to 4 carbonatoms.

The sodium or potassium compounds are preferably used, the hydroxides,amides and alcoholates thereof are of special interest in practice.Mixture thereof may, of course, also be used.

The alkaline condensation agents are preferably used in at least theequivalent amount, but also, if necessary, a many times equivalentamount may be used especially if the compounds to be condensated containgroups capable of being hydrolized or if higher temperatures arerequired in which case part of the condensation agent may be consumed byreaction with the solvent.

When the starting compounds to be condensated contain radicals sensitiveto hydrolysis, for example, carboxylic acid ester groups, condensationproducts are isolated, especially at high reaction temperatures, inwhich these groups are present in hydrolysed state, for example, thefree carboxylic acids or the corresponding salts thereof, depending onthe method of working up.

The process of the invention has the special advantage that working isusually possible at smooth reaction conditions. Reaction temperaturesabove 150° C are not necessary, temperatures above 120° C are onlyrequired in exceptional cases.

Frequently, the reaction is carried out at room temperature withoutexternal heating, which especially occurs when using potassiumalcoholates or potassium hydroxide. In some cases it is advantageous oreven necessary to heat the reaction mixture which is advantageouslycovered by nitrogen, slowly to 30° - 120° C and to maintain thattemperature for a certain time.

The essential advantage of the process of the invention is that itsreaction can easily be carried out and that almost quantitative yieldsare obtained especially also in those cases in which the formation ofcarbanions is not especially activated, for example in the case ofcompounds of the general formula (4").

The reaction product can be isolated from the reaction mixture accordingto usual methods known per se.

The compounds of the general formula (1) which can be prepared by thereaction described above are optical brighteners or- if nitro groups arepresent - precursors of brighteners which may be transformed tobrighteners by reduction of the nitro group to the amino group, e.g. bycatalytic hydrogenation. They are also valuable intermediate productsfor a variety of syntheses, for example, for the preparation ofdyestuffs, scintillators and pharmaceutical products and forelectrophotographic coatings. Optical brighteners of this type areknown, for example, from German Offenlegungsschriften Nos. 2,031,774 and2,105,305, pharmaceutical products, for example, from U.S. Pat. No.3,470,192.

The following examples illustrate the invention:

E X A M P L E 1

21.1 g of ω,ω'-bis-(o-formyl-phenoxy)-dibenzyl were heated to the boilwith 4.7 g of aniline and 0.05 g of p-toluene-sulfonic acid in 250 ml oftoluene for 2 hours and the water was separated via a water separator.The mixture was then allowed to cool, the precipitate which had formed,was suction-filtered, washed with methanol and dried at 60° C in vacuo.27.1 of the compound (101) of the formula ##STR15## were obtained havinga melting point of 220°-222° C (after-recrystallization fromdimethylformamide).

In manner analogous to that of compound (101), the azomethinescharacterized in the following table 1 may be synthesized.

                                      Table 1                                     __________________________________________________________________________    No. in                             Melting point                              sequence                                                                           Constitution                  ° C                                                                            Solvent                            __________________________________________________________________________    (102)                                                                               ##STR16##                    195-197 DMF                                (103)                                                                               ##STR17##                    168-165 DMF                                (104)                                                                               ##STR18##                    172,5   DMF                                (105)                                                                               ##STR19##                    185-189 DMF                                (106)                                                                               ##STR20##                    176-180 DMF                                (107)                                                                               ##STR21##                    resinic, not crystalline                   (108)                                                                               ##STR22##                    fair yellow oil                            (109)                                                                               ##STR23##                    79-81   from n-butanol                     (110)                                                                               ##STR24##                    125-125,5                                                                             from n-butanol                     (111)                                                                               ##STR25##                    132-134 crude product                      (112)                                                                               ##STR26##                    87-95   (crude product)                    (112a)                                                                              ##STR27##                    167-169                                    (112b)                                                                              ##STR28##                    160-163                                    (112c)                                                                              ##STR29##                    179-181                                    __________________________________________________________________________

An isolation of the intermediate or purification of the azomethines isgenerally, however, not necessary. Preferably, the solvents used for thepreparation of the azomethines are distilled off in vacuo, then replacedby a suitable dipolar solvent and the ring closure reactions describedin Example 2 to 6 are immediately carried out.

E X A M P L E 2

31.4 g of the compound (109) were dissolved at room temperature in 250ml of dimethylformamide, 6 g of potassium hydroxide (pulverized, about95%) were added and the mixture was stirred for 45 minutes withoutexternal heating. Then, the reaction mixture was stirred into 500 ml ofice water and the mixture was neutralized with 2 N HCL. The mixture wassuction-filtered, the filter residue washed with water and dried at 60°C in vacuo. 21.5 g of the crude product of the formula (113) ##STR30##were obtained which had a melting point of 137°-139° C.

The compound was purified by recrystallization from gasoline (meltingrange: 100°-150° C) and then had a melting point of 141.5°-142.5° C.

E X A M P L E 3

57.2 g of the compound (101) were suspended in 400 ml of dimethylformamide, 12.55g of potassium hydroxide (pulverized, about 90%) wereadded and the reaction mixture was slowly heated to 100°-120° C. Thistemperature was maintained for 3 hours. Then the batch was allowed tocool to room temperature and the precipitate which had formed, wassuctionfiltered. The filter residue was washed with dimethyl formamide,then with water until it became neutral and then dried at 60° C invacuo. 36 g of crude product of the formula (114) ##STR31## wereobtained which could be purified by recrystallization fromα-chloronaphthalene.

Melting point: > 350° C. C₂₈ H₁₈ O₂ Calculated: C 87.9, H 4.79. (386.45)Found: 87.7, H 4.80. λmax. (absorption/DMF): 351 nm, ε = 7.06 . 10⁴.

E X A M P L E 4

36.3 g of the compound (110) were dissolved in 400 ml ofN,N-dimethylacetamide, 12.2 g of potassium tertiary butylate were addedand the mixture was heated to 80°-90° C for 2 hours while stirring.After cooling, it was worked up as described in example 2. 26 g of crudeproduct of the formula (115) ##STR32## were obtained which could bepurified by recrystallization from n-butanol while adding activecharcoal. Melting point: 176°-177° C.

E X A M P L E 5

40.3 g of the compound (111) were dissolved in 400 ml of dimethylformamide, 7 g of potassium hydroxide (pulverized, about 85%) wereadded, the mixture was stirred at 60° C for 30 minutes, then at 115° Cfor 60 minutes. It was cooled in the ice bath to about 5° C and thepecipitate which had formed, was suction-filtered. It was first washedwith methanol, then with water. After drying at 60° C in vacuo, 30.5 gof the crude product of the formula (116) ##STR33## were obtained, whichwere recrystallized from dimethyl formamide with the addition of activecharcoal. Melting point: 308°-309° C

E X A M P L E 6

37.7 g of the compound (112) were dissolved in 400 ml ofhexamethyl-phosphoric acid trisamide and 7 g of sodium hydroxide wereadded. The mixture was stirred at 60° C for 2 hours and working upfollowed as described in example 2. So, 25 g of crude product of theformula (117) ##STR34## were obtained which had a melting point of 171°C.

In a manner analogous to that described in the preceding examples thecompounds listed in the following table, were prepared.

                                      TABLE 2                                     __________________________________________________________________________                                       Melting      alkali reaction               No. in                             point   Solvent                                                                            metal  temperature            sequence                                                                           Constitution                  ° C                                                                            *    compound                                                                             ° C             __________________________________________________________________________    118                                                                                 ##STR35##                    173-175 DEF  NaOH   40                     119                                                                                 ##STR36##                    218-220 DMF  KOH    25                     120                                                                                 ##STR37##                    124-125 DMF  KOH    100                    121                                                                                 ##STR38##                    199-200 HMPT KOH    25                     122                                                                                 ##STR39##                    126-128 DMA  KOH    25                     123                                                                                 ##STR40##                    114.5   DMF  KO-tert.- butylate                                                                   25                     124                                                                                 ##STR41##                    35-36   DMF  KO-tert.- butylate                                                                   120                    125                                                                                 ##STR42##                    222-223 DMF  NaOH   90                     126                                                                                 ##STR43##                    195     DMF  NaOH   25                     127                                                                                 ##STR44##                    140     DMF  KOH    25                     128                                                                                 ##STR45##                    197-198 DMF  KOH    100                    129                                                                                 ##STR46##                    145     DMF  KOH    110                    130                                                                                 ##STR47##                    290     DMF  KOH    110                    131                                                                                 ##STR48##                    204     DMF  KOH    90                     132                                                                                 ##STR49##                    298     DMF  KOH    90                     133                                                                                 ##STR50##                    171-172.5                                                                             DMF  KOH    90                     134                                                                                 ##STR51##                    144-145.5                                                                             DMF  NaOH   90                     135                                                                                 ##STR52##                    127-128 DMF  NaOH   90                     136                                                                                 ##STR53##                    170-172 DMF  KOH    90                     137                                                                                 ##STR54##                    193-194 DMF  KOH    90                     138                                                                                 ##STR55##                    >350    DMA  NaOH   125                    139                                                                                 ##STR56##                    >350    DMA  NaOH   125                    140                                                                                 ##STR57##                    >350    DMA  NaOH   125                    141                                                                                 ##STR58##                    >350    HMPT KO-tert.- butylate                                                                   125                    142                                                                                 ##STR59##                    >350    DMA  KOH    120                    143                                                                                 ##STR60##                    >350    DMF  KOH    120                    144                                                                                 ##STR61##                    121     HMPT KOH    80                     __________________________________________________________________________     *DMF = dimethyl formamide                                                     DEF = diethyl formamide                                                       DMA = dimethyl acetamide                                                      HMPT = hexamethyl-phosphoric acid trisamide.                             

I claim:
 1. A compound of the formula ##STR62## in which A is phenyl ornaphthyl which is unsubstituted or substituted by halogen, lower alkyl,lower alkoxy, lower alkylene forming an annellated ring, or phenyl, R ishydrogen, lower alkyl or phenyl, E is lower tertiary alkyl, phenyl,chlorophenyl, lower alkyl phenyl, lower hydroxyalkyl phenyl or naphthyland D' is phenyl, naphthyl, styryl, or a bivalent group selected fromethenylene, phenylene and p,ω-styrylene which bivalent group issubstituted by a group of the formula ##STR63## in which A, R and E areas defined above, which radical D' may be substituted by carboxy, lowercarboalkoxy, cyano, or nitro.
 2. A compound as defined in claim 1,wherein A is phenyl, mono- or di-(lower alkyl)-phenyl, indanyl,tetrahydronaphthyl or naphthyl; R is hydrogen or methyl; E is phenyl orchlorophenyl and D' is phenyl, cyanophenyl, carboxyphenyl, lowercarboalkoxyphenyl, or nitrophenyl; naphthyl, cyanonaphthyl,carboxynaphthyl, lower carboalkoxynaphthyl; styryl, or a bivalent groupselected from ethenylene, phenylene and p,ω-styrylene which bivalentgroup is substituted by a group of the formula ##STR64## in which A, Rand E are as defined above.
 3. A compound as defined in claim 1, whereinA is phenyl, tolyl, xylyl, tert.-butyl phenyl, indanyl or naphthyl, R ishydrogen or methyl, E is phenyl or chlorophenyl and D' is phenyl,cyanophenyl or styryl ##STR65##
 4. A compound as defined in claim 1,wherein R is hydrogen and E is phenyl.
 5. The compound as defined inclaim 1, wherein A is phenyl, R is hydrogen, E is phenyl and D' isp-cyanophenyl.